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Humanized Anti-il-20 antibody and uses thereof

Active Publication Date: 2013-11-28
LBL BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present disclosure is about two humanized anti-IL-20 antibodies that have high affinity to IL-20 and can be used to treat IL-20-related diseases, such as osteoporosis. These antibodies can be full-length antibodies, antigen-binding fragments, or single-chain antibodies. The disclosure also includes nucleic acids and vectors that encode the antibodies, as well as methods for treating diseases associated with the IL-20-mediated signaling pathway by administering the humanized anti-IL-20 antibodies. The technical effect of the invention is the development of effective tools for targeting IL-20 and treating related diseases.

Problems solved by technology

However, one problem associated with the use of non-human antibodies as therapeutic agents is their immunogenicity, which substantially reduces the in vivo effectiveness of such antibodies.

Method used

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  • Humanized Anti-il-20 antibody and uses thereof
  • Humanized Anti-il-20 antibody and uses thereof
  • Humanized Anti-il-20 antibody and uses thereof

Examples

Experimental program
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example 1

Preparation of Humanized Anti-IL-20 Antibodies

[0069]Exemplary humanized anti-IL-20 antibodies HL1 and HL2 were prepared as follows, using mouse monoclonal antibody 7E (mAb 7E) as the parent antibody. mAb 7E was described in U.S. Pat. Nos. 7,435,800 and 7,786,274, both of which are incorporated by reference herein. The amino acid sequences of the VH and VL chains of mAb 7E are shown below:

Amino acid sequence of mAb 7E VH:(SEQ ID NO: 9)M Y L G L N Y V F I V F L L N G V Q S E L K L E E S G G G L V Q P G G S M K L S C A A SG F T F S D A W M D W V R Q S P E K G L E W I A E I R S K A N N Y A T Y F A E S V KG R F T I S R D D S K S G V Y L Q M N N L R A E D T G I Y F C T K L S L R Y W F F D VW G A G T T V T V S SAmino acid sequence of mAb 7E VL:(SEQ ID NO: 10)M M S P A Q F L F L L V L W I R E T N G D F V M T Q T P L T L S V T I G Q P A S I S C KS S Q S L L D S D G K T Y L N W L L Q R P G Q S P K H L I Y L V S K L D S G V P D R FT G S G S G T D F T L R I S R V E A E D L G V Y Y C W Q S T H F...

example 2

Biological Function Analysis of Humanized Anti-IL-20 Antibody

[0080]The antigen binding affinity of the humanized anti-IL-20 antibodies prepared in Example 1 above, as well as those of the parent antibody and a chimeric antibody derived therefrom, was examined via the standard BIOCORE technology following the manufacturer's protocol. The results are shown below:

[0081]Parent antibody 7E: 6.8×10−10

[0082]Humanized antibody HL1: 3.6×10−9

[0083]Humanized antibody HL2: 1.2×10−9

[0084]Chimeric antibody: 4.2×10−9

[0085]Unexpected, both humanized antibodies HL1 and HL2 showed antigen-binding affinities similar to that of the parent antibody. In particular, humanized antibody HL2 showed an antigen-binding affinity higher than the chimeric antibody.

[0086]The biological function of the humanized anti-IL-20 antibody noted above was analyzed via an inhibition of osteoclast differentiation assay. The parent mouse 7E antibody and a chimeric antibody derived therefrom were used as controls. The chim...

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Abstract

The present disclosure provides humanized antibodies specific to human interleukin 20 (IL-20) and uses thereof in treating diseases associated with the IL-20 signaling pathway, e.g., osteoporosis, inflammatory disease (e.g., rheumatoid arthritis), cancer, stroke, and renal failure.

Description

BACKGROUND OF THE INVENTION[0001]Interleukin 20 (IL-20), a pleiotropic inflammatory cytokine, is a member of the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26. IL-20 is expressed in monocytes, epithelial cells, and endothelial cells. It acts on multiple types of cells via activating a heterodimer receptor complex of either IL-20R1 / IL-20R2 or IL-22R1 / IL-20R2. IL-20 has been found to be involved in various diseases, such as psoriasis, rheumatoid arthritis, atherosclerosis, ischemic stroke, osteoporosis, and renal failure. Certain anti-IL-20 antibodies have been reported to possess therapeutic effects in treating IL-20 associated diseases, e.g., osteoporosis and rheumatoid arthritis. U.S. Pat. Nos. 7,435,800, 7,611,705, 7,786,274, 7,837,994, 8,012,478; and US Patent Publications 20110305699 and 20090048432.[0002]Monoclonal antibodies derived from non-human species are routinely used in biochemistry, molecular biology, and medical research. In addition, they ...

Claims

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Application Information

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IPC IPC(8): A61K39/395C12N15/13A61P19/10C12N15/63A61P19/02A61P35/00A61P25/00A61P13/12C07K16/24A61P29/00
CPCA61P13/12A61P19/02A61P19/10A61P25/00A61P29/00A61P35/00C07K16/244C07K2317/24C07K2317/76C07K2317/92A61K39/3955A61K45/06
Inventor CHANG, MING-SHITSURUSHITA, NAOYAKUMAR, SHANKAR
Owner LBL BIOTECH INC